Project Summary Amyloid beta peptides, which accumulate and appear to cause Alzheimer's disease, appear to have been modified to a substantial degree by fatty acid oxidation products. These and other observations suggest that a membrane-mediated process is operating in Alzheimer's disease with the potential to explain neuronal loss, fibril formation, and the lack of correlation between plaque deposition and the clinical severity of AD. This is a proposal to quantify post-translationally modified forms of the amyloid beta protein, and search for similar modifications of other proteins in human brain tissue. Notably, this proposal will make use of novel biochemical assays and approaches to identify and quantify these modifications.